Recombinant viral vector systems expressing exogenous feline paramyxovirus genes and vaccines made therefrom

Abstract

The present invention relates to exogenous feline paramyxovirus genes, which are expressed from recombinant viral vector systems.

The invention claimed is: 
     
       1. A viral vector, comprising at least one exogenous antigen encoding sequence relating to/of at least one pathogen infecting felines, wherein the at least one pathogen infecting felines is feline paramyxovirus is selected from the group consisting of:
 (a) a feline paramyxovirus type 2 (FPaV-2), the genome of which comprises a ribonucleic acid complementary to the nucleic acid sequence selected from the group consisting of:
 (i) a nucleic acid sequence according to SEQ ID NO: 1, 
 (ii) a nucleic acid sequence which is at least 85% identical to SEQ ID NO:1 over the whole length of SEQ ID NO:1; 
 
 (b) feline paramyxovirus type 2 (FPaV-2) as deposited at Collection Nationale de Culture de Microorganismes (CNCM) under accession number CNCM I-5123; 
 (c) a feline paramyxovirus type 2 (FPaV-2), the genome of which comprises a ribonucleic acid complementary to the nucleic acid sequence selected from the group consisting of:
 (i) a nucleic acid sequence according to SEQ ID NO: 2, 
 (ii) a nucleic acid sequence which is at least 85% identical to SEQ ID NO:2 over the whole length of SEQ ID NO:2; 
 
 (d) a feline morbillivirus (FeMoV), the genome of which comprises a ribonucleic acid complementary to the nucleic acid sequence selected from the group consisting of:
 (i) a nucleic acid sequence according to SEQ ID NO: 3, 
 (ii) a nucleic acid sequence which is at least 94% identical to SEQ ID NO:3 over the whole length of SEQ ID NO:3. 
 
 
     
     
       2. The viral vector according to  claim 1 , wherein the viral vector is selected from the group consisting of: avipox virus viral vector, canine morbillivirus viral vector, herpes virus viral vector. 
     
     
       3. The viral vector according to  claim 1 , wherein the viral vector is an attenuated canarypox vector. 
     
     
       4. The viral vector according to  claim 1 , wherein the at least one exogenous antigen encoding sequence is selected from the group consisting of: hemagglutinin protein (H) encoding sequence, matrix protein (M) encoding sequence, fusion protein (F) encoding sequence, nucleocapsid protein (N) encoding sequence, phosphoprotein (P) encoding sequence, RNA-dependent RNA polymerase protein (L) encoding sequence. 
     
     
       5. The viral vector according to  claim 4 , wherein the at least one exogenous antigen encoding sequence is a hemagglutinin protein (H) encoding sequence and the hemagglutinin protein (H) encoding sequence comprises a nucleic acid sequence which is at least 70% identical to SEQ ID NO:4, or SEQ ID NO: 5; or wherein the at least one exogenous antigen encoding sequence is a hemagglutinin protein (H) encoding sequence and the hemagglutinin protein (H) encoding sequence comprises a nucleic acid sequence encoding a polypeptide having an amino acid sequence which is at least 85% identical to SEQ ID NO:6. 
     
     
       6. The viral vector according to  claim 4 , wherein the at least one exogenous antigen encoding sequence is a matrix protein (M) encoding sequence and the matrix protein (M) encoding sequence comprises a nucleic acid sequence which is at least 70% identical to SEQ ID NO:7 or SEQ ID NO:8, or wherein the at least one exogenous antigen encoding sequence is a matrix protein (M) encoding sequence and the matrix protein (M) encoding sequence comprises a nucleic acid sequence encoding a polypeptide having an amino acid sequence which is at least 85% identical to SEQ ID NO:9. 
     
     
       7. The viral vector according to  claim 4 , wherein the at least one exogenous antigen encoding sequence is a fusion protein (F) encoding sequence and the fusion protein F) encoding sequence comprises a nucleic acid sequence which is at least 70% identical to SEQ ID NO:10 or SEQ ID NO:11, or wherein the at least one exogenous antigen encoding sequence is a fusion protein (F) encoding sequence and the fusion protein (F) encoding sequence comprises a nucleic acid sequence encoding a polypeptide having an amino acid sequence which is at least 85% identical to SEQ ID NO:12. 
     
     
       8. The viral vector according to  claim 1 , wherein the viral vector comprises two or more exogenous antigen encoding sequences, a hemagglutinin protein (H) encoding sequence and a matrix protein (M) encoding sequence, or a hemagglutinin protein (H) encoding sequence and a fusion protein (F) encoding sequence, or a matrix protein (M) encoding sequence and a fusion protein (F) encoding sequence, or a hemagglutinin protein (H) encoding sequence and a matrix protein (M) encoding sequence and a fusion protein (F) encoding sequence. 
     
     
       9. The viral vector according to  claim 1 , wherein the viral vector comprises two exogenous antigens, wherein said exogenous antigens encode for the same protein derived from two distinct viral species, wherein the first exogenous antigen is derived from the feline paramyxovirus type 2 (FPaV-2), and wherein the second exogenous antigen is derived from the feline morbillivirus. 
     
     
       10. The viral vector according to  claim 1 , wherein the viral vector is an ALVAC vector and wherein the at least one exogenous antigen encoding sequence is inserted in at least one insertion locus, in a non-essential region of the viral vector genome; or wherein the at least one exogenous antigen encoding sequence is inserted in two or more insertion loci; and/or wherein the at least one insertion locus is insertion locus C3; and/or wherein the viral vector comprises flanking sequences of the insertion locus C3, wherein the flanking sequences are selected from the group comprising SEQ ID NO:45 (C3 flanking region left arm) and SEQ ID NO:46 (C3 flanking region right arm); or wherein the at least one insertion locus is insertion locus C5; and/or wherein the viral vector comprises flanking sequences of the insertion locus C5, wherein the flanking sequences are selected from the group comprising SEQ ID NO:47 (C5 flanking region left arm) and SEQ ID NO:48 (C5 flanking region right arm). 
     
     
       11. The viral vector according to  claim 1 , wherein the viral vector comprises a nucleic acid sequence which is at least 70% identical to the nucleic acid sequence selected from the group consisting of SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:95, or is the nucleic acid sequence selected from the group consisting of: SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:95. 
     
     
       12. The viral vector according to  claim 1 , wherein the feline is a cat. 
     
     
       13. An isolated mammalian host cell characterized in that it comprises the viral vector according to  claim 1 . 
     
     
       14. An immunogenic composition comprising
 (a) the viral vector according to  claim 1 , and 
 (b) optionally a pharmaceutical- or veterinary-acceptable carrier or excipient. 
 
     
     
       15. A vaccine or pharmaceutical composition comprising
 (a) the viral vector according to  claim 1 , and 
 (b) a pharmaceutical- or veterinary-acceptable carrier or excipient, 
 (c) optionally said vaccine or pharmaceutical composition further comprising an adjuvant. 
 
     
     
       16. A method for the preparation of an immunogenic composition or a vaccine for reducing the incidence and/or the severity of one or more clinical signs associated with or caused by an infection with at least one pathogenic paramyxovirus, comprising the following steps:
 (a) infecting an isolated mammalian host cell with the viral vector according to  claim 1 , 
 (b) cultivating the infected cells under suitable conditions, 
 (c) collecting infected cell cultures, 
 (d) optionally purifying the collected infected cell cultures of step (c), 
 (e) optionally mixing said collected infected cell culture with a pharmaceutically acceptable carrier. 
 
     
     
       17. A method of treating, and/or inhibiting infection, and/or reducing or preventing the clinical signs or disease caused by an infection with at least one pathogenic paramyxovirus in a feline, comprising administering to the feline an effective amount of the immunogenic composition according to  claim 16  or the vaccine or pharmaceutical composition according to  claim 15 , wherein the at least one pathogenic paramyxovirus is a feline paramyxovirus, and wherein said clinical signs or disease caused by an infection with at least one pathogenic paramyxovirus or said infection are selected from the group consisting of: viremia, fever, virus shedding in the environment, infections and diseases of the urogenital system. 
     
     
       18. A method of immunizing a feline against a clinical disease caused by at least one pathogenic paramyxovirus in said feline, said method comprising the step of administering to the feline the immunogenic composition according to  claim 16  or the vaccine or pharmaceutical composition according to  claim 15 , wherein said immunogenic composition or vaccine fails to cause clinical signs of infection but is capable of inducing an immune response that immunizes the feline against pathogenic forms of said at least one paramyxovirus, wherein said clinical disease or said clinical signs of infection are selected from the group comprising of: viremia, fever, virus shedding in the environment, infections of the urogenital system, infections of the urinary system, kidney disease, chronic kidney disease (CKD), inflammation of the renal tubules and renal interstitial tissue, idiopathic tubulointerstitial nephritis (TIN). 
     
     
       19. The viral vector according to  claim 9 , wherein the one strain of “the hemagglutinin protein (H) encoding sequence of one strain” is a hemagglutinin protein (H) encoding sequence and the hemagglutinin protein (H) encoding sequence comprises a nucleic acid sequence which is at least 70% identical to SEQ ID NO:4 or 19 or is selected from the group consisting of: SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:19; and the another strain of the “hemagglutinin protein (H) encoding sequence of another strain” is a hemagglutinin protein (H) encoding sequence and the hemagglutinin protein (H) encoding sequence comprises a nucleic acid sequence which is at least 70% identical to SEQ ID NO:31 or 94 or is selected from the group consisting of: SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:94. 
     
     
       20. The method of  claim 17 , wherein the infections and disease of the urogenital system are selected from the group comprising, infections of the urinary system, kidney disease, chronic kidney disease (CKD), inflammation of the renal tubules and renal interstitial tissue, and idiopathic tubulointerstitial nephritis (TIN). 
     
     
       21. The viral vector according to  claim 1 , wherein the viral vector is an attenuated fowlpox vector. 
     
     
       22. The viral vector according to  claim 3 , wherein the attenuated canarypox vector is ALVAC. 
     
     
       23. The viral vector according to  claim 22 , wherein the ALVAC is selected from the group comprising ALVAC-1 or ALVAC-2, and ALVAC as deposited under the terms of the Budapest Treaty at the American Type Culture Collection (ATCC) under accession number VR-2547. 
     
     
       24. The viral vector according to  claim 21 , wherein the attenuated fowlpox vector is TROVAC. 
     
     
       25. The viral vector according to  claim 24 , wherein the TROVAC is TROVAC as deposited under the terms of the Budapest Treaty at the American Type Culture Collection (ATCC) under accession number VR-2553. 
     
     
       26. The viral vector according to  claim 9 , wherein the first exogenous antigen is derived from the feline paramyxovirus type 2 (FPaV-2) Gordon strain or the FPaV-2 TV25 strain. 
     
     
       27. The viral vector according to  claim 9 , wherein the second exogenous antigen is derived from the feline morbillivirus Lapön strain.